Heparin is normally provided by the pharmaceutical industry as an alkali metal (for example, primarily sodium) or alkaline earth (for example calcium) salt in view of the limited stability of the free acid form of heparin. The salts are most commonly provided for pharmaceutical use in the form of solutions. Solid heparin salts tend to be somewhat hygroscopic and gradually absorb water unless maintained in a low humidity environment. They are amorphous rather than crystalline and are available as fine powders.
Both the solution and solid forms of the heparin salts are conventionally utilized in blood-gas analyses wherein they serve as anticoagulants to maintain liquidity of the blood being tested. Blood-gas analyses are widely used in diagnostic medicine, oxygen and carbon dioxide contents of blood samples being of particular importance. From such measurements, a physician may obtain accurate oxygen level readings from which he may more accurately anticipate the patient's supplementary oxygen needs.
The measurement of arterial blood gas normally involves drawing a sample of blood into a syringe containing an anticoagulant and then injecting the blood sample into an analyzing instrument. The anticoagulant is used to maintain the liquidity of the blood sample so that the partial pressures of the blood gases are at substantially the same level as when initially drawn.
Even though the procedure seems simple and straightforward there are numerous opportunities for sources of error to be introduced. One particular source of error has been found to result from the method in which the anticoagulant is added to the drawn blood samples.
There are three primary methods for the introduction of an anticoagulant such as heparin into the blood samples. The first method involves the drawing of a quantity of heparin solution into a syringe in order to wet the interior walls. A substantial portion of the excess heparin is ejected and the blood is then drawn into the syringe from the patient. The blood when drawn mixes with the heparin solution to prevent coagulation. The error in this method results from the fact that an indeterminate amount of heparin solution remains in the syringe interior, needle hub and cannula. As a result, the drawn blood sample is diluted by an indeterminate amount of heparin solution which in most cases leads to less accurate blood gas data.
A second method involves the use of preheparinized syringes. These syringes are prepared by depositing a lyophilized heparin on the internal surface of the syringe. They have been found to vary in the location and the amount of heparin on the syringe barrel wall. Also, the deposited heparin dissolution rate into the blood is slower than optimal and is unpredictable. This slow dissolution rate combined with the variability in amount allows partial blood coagulation thereby introducing a source of error into the analysis. Because lyophilized heparin is more difficult and complex to manufacture and use than a heparin solution, these preheparinized syringes have been found to be much more costly without proportionately minimizing the amount of potential error.
A third method recently introduced comprises placing an anticoagulant tablet in the hub of the needle of the syringe used to obtain a blood sample from a patient. The blood flowing through the needle and into the syringe dissolves the tablet and the blood is heparinized. These tablets are comprised of a salt of heparin, a tablet binder and a pH controlling substance. Although the rate of dissolution of these tablets is fast compared to the heparinized syringe, the time required for disintegration is up to 20 seconds, and for complete dissolution up to two minutes. Also, the use of these tablets requires a mixing step after the blood is drawn into the syringe. The tablet binder and pH controlling substance are adjuvants requiring added cost and additional manufacturing complexities.